Function of Platelet-Induced Epithelial Attachment at Titanium Surfaces Inhibits Microbial Colonization.

The aim of this study was to evaluate the barrier function of platelet-induced epithelial sheets on titanium surfaces. The lack of functional peri-implant epithelial sealing with basal lamina (BL) attachment at the interface of the implant and the adjacent epithelium allows for bacterial invasion, which may lead to peri-implantitis. Although various approaches have been reported to combat bacterial infection by surface modifications to titanium, none of these have been successful in a clinical application. In our previous study, surface modification with protease-activated receptor 4-activating peptide (PAR4-AP), which induced platelet activation and aggregation, was successful in demonstrating epithelial attachment via BL and epithelial sheet formation on the titanium surface. We hypothesized that the platelet-induced epithelial sheet on PAR4-AP-modified titanium surfaces would reduce bacterial attachment, penetration, and invasion. Titanium surface was modified with PAR4-AP and incubated with platelet-rich plasma (PRP). The aggregated platelets released collagen IV, a critical BL component, onto the PAR4-AP-modified titanium surface. Then, human gingival epithelial cells were seeded on the modified titanium surface and formed epithelial sheets. Green fluorescent protein (GFP)-expressing Escherichia coli was cultured onto PAR4-AP-modified titanium with and without epithelial sheet formation. While Escherichia coli accumulated densely onto the PAR4-AP titanium lacking epithelial sheet, few Escherichia coli were observed on the epithelial sheet on the PAR4-AP surface. No bacterial invasion into the interface of the epithelial sheet and the titanium surface was observed. These in vitro results indicate the efficacy of a platelet-induced epithelial barrier that functions to prevent bacterial attachment, penetration, and invasion on PAR4-AP-modified titanium.

Nodules behind the ears: IgG4-related skin disease.

A 53-year-old healthy factory worker consulted our hospital complaining of small nodules of similar size, shape and location on both ears. The nodules revealed focal and massive infiltration of lymphocytes, plasma cells and eosinophils with fibrosis. They had no specific structure on pathological staining with haematoxylin and eosin. Immunostaining for IgG4 revealed that a large majority of the IgG+ cells were positive for IgG4. The ratio of IgG4+ to IgG+ plasma cells was approximately 40%. IgG4+ plasma cells were present at approximately 250 per high-power field. The patient was diagnosed with IgG4-related skin disease without multiple organ involvement in the systemic syndrome of IgG4-related diseases. Because the patient was a factory worker and exposed to an environment of metallic dust, a skin patch test that included a metal series was performed. Zinc and manganese produced positive reactions. Because only skin lesions were observed in this case, not multiple organ involvement, tissue infiltration by IgG4+ plasma cells might have resulted from continuous sensitization to zinc and/or manganese.

Aerobic exercise training-induced left ventricular hypertrophy involves regulatory MicroRNAs, decreased angiotensin-converting enzyme-angiotensin ii, and synergistic regulation of angiotensin-converting enzyme 2-angiotensin (1-7).

Aerobic exercise training leads to a physiological, nonpathological left ventricular hypertrophy; however, the underlying biochemical and molecular mechanisms of physiological left ventricular hypertrophy are unknown. The role of microRNAs regulating the classic and the novel cardiac renin-angiotensin (Ang) system was studied in trained rats assigned to 3 groups: (1) sedentary; (2) swimming trained with protocol 1 (T1, moderate-volume training); and (3) protocol 2 (T2, high-volume training). Cardiac Ang I levels, Ang-converting enzyme (ACE) activity, and protein expression, as well as Ang II levels, were lower in T1 and T2; however, Ang II type 1 receptor mRNA levels (69% in T1 and 99% in T2) and protein expression (240% in T1 and 300% in T2) increased after training. Ang II type 2 receptor mRNA levels (220%) and protein expression (332%) were shown to be increased in T2. In addition, T1 and T2 were shown to increase ACE2 activity and protein expression and Ang (1-7) levels in the heart. Exercise increased microRNA-27a and 27b, targeting ACE and decreasing microRNA-143 targeting ACE2 in the heart. Left ventricular hypertrophy induced by aerobic training involves microRNA regulation and an increase in cardiac Ang II type 1 receptor without the participation of Ang II. Parallel to this, an increase in ACE2, Ang (1-7), and Ang II type 2 receptor in the heart by exercise suggests that this nonclassic cardiac renin-angiotensin system counteracts the classic cardiac renin-angiotensin system. These findings are consistent with a model in which exercise may induce left ventricular hypertrophy, at least in part, altering the expression of specific microRNAs targeting renin-angiotensin system genes. Together these effects might provide the additional aerobic capacity required by the exercised heart.

Influence of angiotensinogen and angiotensin-converting enzyme polymorphisms on cardiac hypertrophy and improvement on maximal aerobic capacity caused by exercise training.

BACKGROUND: The allele threonine (T) of the angiotensinogen has been associated with ventricular hypertrophy in hypertensive patients and soccer players. However, the long-term effect of physical exercise in healthy athletes carrying the T allele remains unknown. We investigated the influence of methionine (M) or T allele of the angiotensinogen and D or I allele of the angiotensin-converting enzyme on left-ventricular mass index (LVMI) and maximal aerobic capacity in young healthy individuals after long-term physical exercise training. DESIGN: Prospective clinical trial. METHODS: Eighty-three policemen aged between 20 and 35 years (mean+/-SD 26+/-4.5 years) were genotyped for the M235T gene angiotensinogen polymorphism (TT, n = 25; MM/MT, n = 58) and angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism (II, n = 18; DD/DI, n = 65). Left-ventricular morphology was evaluated by echocardiography and maximal aerobic capacity (VO2peak) by cardiopulmonary exercise test before and after 17 weeks of exercise training (50-80% VO2peak). RESULTS: Baseline VO2peak and LVMI were similar between TT and MM/MT groups, and II and DD/DI groups. Exercise training increased significantly and similarly VO2peak in homozygous TT and MM/MT individuals, and homozygous II and DD/DI individuals. In addition, exercise training increased significantly LVMI in TT and MM/MT individuals (76.5+/-3 vs. 86.7+/-4, P = 0.00001 and 76.2+/-2 vs. 81.4+/-2, P = 0.00001, respectively), and II and DD/DI individuals (77.7+/-4 vs. 81.5+/-4, P = 0.0001 and 76+/-2 vs. 83.5+/-2, P = 0.0001, respectively). However, LVMI in TT individuals was significantly greater than in MM/MT individuals (P = 0.04). LVMI was not different between II and DD/DI individuals. CONCLUSION: Left-ventricular hypertrophy caused by exercise training is exacerbated in homozygous TT individuals with angiotensinogen polymorphism.

Determinants of hyperleptinaemia in an African population.

OBJECTIVE: To examine the determinants for elevated plasma leptin concentration in normal weight (NW), obese (OB), and morbidly obese (MO) individuals in Tanzania. DESIGN: Cross-sectional epidemiological study, the CARDIAC study. SETTING: Three areas in Tanzania; Dar es Salaam, urban (U), Handeni, rural (R) and Monduli, pastoralists (P), in August 1998. SUBJECTS: Five hundred and forty five participants from a random sample of 600 people aged 46-58 years. MAIN OUTCOME MEASURES: Plasma leptin concentrations, height, weight, body mass index (BMI), lipid profiles, haemoglobin A1c (HBA1c), and blood pressure (BP). RESULTS: Plasma leptin concentrations were higher in women than in men (women; 16.0 ng/mL, men; 3.1 ng/mL; p<0.0001). Women showed a higher mean body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) than men. In both genders, plasma leptin concentration, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), systolic BP (SBP) and diastolic BP (DBP) were significantly higher in OB than in NW participants. MO women had significantly higher leptin concentration, SBP and DBP compared with the other two groups. In NW men, log leptin concentrations showed a direct correlation with weight, BMI, HBA1c, TC, LDL-C, TG, SBP and DBP (all p<0.0001 except TG; p<0.001), while among NW women and OB men, weight and BMI correlated positively with log leptin (all p<0.05). OB women observed a positive correlation between log leptin and weight, BMI and LDL-C. Regression analysis indicated that among NW subjects, gender, BMI and TC explained 53.9% of the variation in log leptin. In OB subjects, gender, BMI and LDL-C explained 51.7% of the variability in leptin levels. No relationship was found between log leptin and CVD risk factors among MO subjects. CONCLUSION: The most important determinants for hyperleptinaemia in NW participants were gender, BMI, TC, while in addition to these LDL-C, was an important determinant of leptin concentration in OB individuals. In MO women, the high leptin concentrations did not reflect the amount of adipose stores.

Amelioration of hyperalgesia by kinin receptor antagonists or kininogen deficiency in chronic constriction nerve injury in rats.

OBJECTIVE: The present study was designed to examine the involvement of bradykinin in thermal and mechanical hyperalgesia induced by chronic constriction nerve injury (CCI) using B1 and B2 receptor antagonists and mutant kininogen-deficient rats. METHODS: Sprague-Dawley (SD) rats and Brown Norway (B/N-) rats given CCI treatment on day 0, were used as a model of neuropathic pain. Either a kinin B1 antagonist des-Arg9-[Leu8]-bradykinin or the receptor B2 antagonist HOE-140 was constantly infused into the left jugular vein of SD rats on days 15 to 22 after CCI. Vehicle-treated rats and sham-operated rats without nerve injury were also prepared as controls. In all rats, we observed pain behavior, and measured the latency period of paw withdrawal from the thermal stimuli and, with von Frey filaments, the mechanical pain threshold, before surgery and on days 14 and 22 after CCI. B/N-Katholiek rats, which congenitally lack plasma kininogen and release no kinin, were also tested for hyperalgesic parameters. Expression of kinin receptor mRNA in the dorsal root ganglia was detected by RT-PCR. RESULTS: Most of the rats (88%) showed some pain behavior, which was reduced to 67% by a B1 antagonist and to 57% by a B2 antagonist infused between days 15 to 22. Thermal hyperalgesia was significantly reduced from 7.25 +/- 0.41 sec (mean +/- SEM) to 8.36 +/- 0.41 sec in paw withdrawal latency on day 22 by a B1 antagonist and from 7.24 +/- 0.19 sec to 8.23 +/- 0.21 sec by a B2 antagonist (P < 0.05). Mechanical hyperalgesia was also ameliorated from 0.02 +/- 0.007 g force to 0.16 +/- 0.08 g force in pain threshold by a B1 antagonist and from 0.03 +/- 0.007 g force to 0.10 +/- 0.003 g force on day 22 by a B2 antagonist. Moreover, deficient B/N-Katholiek rats showed a low incidence of thermal and mechanical hyperalgesia on day 14. Expression of both B1 and B2 receptor mRNAs was detected in the lumbar dorsal ganglia ipsilateral to the site of the nerve injury. CONCLUSION: These data suggests that kinin were at least partly involved in yielding nociceptor hypersensitivity up to day 14 after CCI. Bradykinin and its B1 and B2 receptors were involved in the maintenance of hyperalgesia.

Polyunsaturated fatty acids induce tight junctions to form in brain capillary endothelial cells.

Tight junctions create a rate-limiting barrier to the diffusion of solutes between vertebrate epithelial cells and endothelial cells. They are also controlled within individual cells by a variety of physiologically relevant signals. We investigated the effects of polyunsaturated fatty acids on the formation of tight junctions in brain capillary endothelial cells, monitoring the transepithelial electrical resistance, and analyzed the expression of occludin messenger RNA. Brain-capillary endothelial cells were grown to confluence on filters and exposed to eicosapentaenoic acids, gamma linolenic acid and linoleic acid. Transepithelial electrical resistance was determined with voltage-measuring electrodes. The messenger RNA expression of occludin was quantitated by real-time quantitative reverse transcriptase-polymerase chain reaction. The basal resistance across monolayers of porcine brain capillary endothelial cells was 83+/-8.1 Omega cm(2). Cells cultured in eicosapentaenoic acids and gamma linolenic acid, but not linolenic acid, displayed a 2.7-fold increase in transepithelial electrical resistance at 10 microM in brain capillary endothelial cells. The expression level of occludin messenger RNA increased markedly immediately after the exposure to eicosapentaenoic acids or gamma linolenic acid. Following an 8 h exposure to exogenous eicosapentaenoic acids or gamma linolenic acid, occludin messenger RNA levels were significantly increased. In addition, the rise in transepithelial electrical resistance induced by eicosapentaenoic acids and gamma linolenic acid was markedly inhibited by the tyrosine kinase inhibitors genistein and PP2 and protein kinase C inhibitor, calphostin C. In contrast, the rise in transepithelial electrical resistance induced by eicosapentaenoic acids and gamma linolenic acid was not inhibited by the PI 3-kinase inhibitor, LY294002. We conclude that eicosapentaenoic acids and gamma linolenic acid increased the transepithelial electrical resistance and the expression of occludin messenger RNA in brain capillary endothelial cells. This gamma linolenic acid and eicosapentaenoic acid induced assembly of tight junction is likely to be regulated by protein kinase C and tyrosine kinase activity.

Obesity and lipid profiles in middle aged men and women in Tanzania.

OBJECTIVE: To examine the relationship between obesity and lipid profiles and to compare the effects of total obesity and central adiposity on lipids in three locations in Tanzania. DESIGN: Cross-sectional epidemiological study. SETTING: Three areas in Tanzania: Dar es Salaam (urban), Handeni (rural) and Monduli (pastoralists), in August 1998. SUBJECTS: Five hundred and forty five men and women from a random sample of 600 people aged 46-58 years. MAIN OUTCOME MEASURES: Mean BMI, waist circumference, WHR, TC, HDL-C, LDL-C, TG and LDL/HDL ratio. Prevalence rates of overweight,obesity, central obesity and dyslipidaemia. RESULTS: As compared to men, women had higher BMI (24.7 versus 22.5 kg/m2, p<0.0001), waist circumference (92.4 versus 89.1 cm, p<0.05), TC (4.9 versus 4.2 mmol/L, p<0.0001) and LDL-C (3.3 versus 2.6 mmol/L, p<0.0001). The urban population demonstrated higher levels of lipid factors than the rural population (TC, men 4.8 mmol/L; women 5.3 mmol/L, p<0.0001; TG, men 3.6 mmol/L; women 3.7 mmol/L, p<0.0001, LDL-C, men 2.8 mmol/L, p<0.0001). BMI and waist circumference correlated positively with serum TC, TG, and LDL-C in both genders. Stepwise regression analysis showed that BMI predicted triglyceride concentration in men (p<0.05) and women (p<0.0001). Waist circumference predicted levels of TC in women only (p<0.0001) and of LDL-C in both genders (men p<0.05, women p<0.0001). The prevalence of overweight, obesity and central obesity were significantly higher in urban than in rural areas in both men and women. Compared to lean subjects, obese men and women had significantly higher mean serum TC, TG, LDL-C and a higher prevalence of dyslipidaemia. The mean levels of TC, TG and LDL cholesterol increased across successive increases in BMI and waist circumference quintiles in both genders. CONCLUSION: Subjects from the urban area had greater lipid abnormalities related to obesity than those from the rural area and that, central adiposity had a greater effect on total cholesterol and LDL cholesterol among women than was BMI.

Coherent gluon production in very-high-energy heavy-ion collisions.

The early stages of a relativistic heavy-ion collision are examined in the framework of an effective classical SU(3) Yang-Mills theory in the transverse plane. We compute the initial energy and number distributions, per unit rapidity, at midrapidity, of gluons produced in high-energy heavy-ion collisions. We discuss the phenomenological implications of our results in light of the recent Relativistic Heavy-Ion Collider data.

Distribution of twenty-four hour urinary taurine excretion and association with ischemic heart disease mortality in 24 populations of 16 countries: results from the WHO-CARDIAC study.

There is considerable interest in the association between taurine (2-aminoethanesufonic acid) and risk of ischemic heart disease (IHD), but little information has been made available on the distribution of taurine in populations around the world. The present study aimed to describe the differences in taurine excretion levels and their associations with IHD mortality rates in 24 populations in 16 countries worldwide. This was a multicenter cross-sectional study. In each center, 100 men and 100 women aged 48-56 years were selected randomly from the local populations. Twenty-four hour urinary taurine excretion was measured using an amino acid analyzer (Hitachi 835, Ibaragi, Japan). Age-adjusted IHD mortality rates in the relevant populations were calculated using the direct standard method. The results indicated that (a) percentiles 25%, 50% and 75% of the distributions of 24-h taurine excretion showed large variations in the study populations. Median values of taurine ranged from 191.6 micromol/day (St John, Canada) to 2,180.6 micromol/day (Beppu, Japan) in males, and from 127.5 micromol/day (Moscow, Russia) to 1,590.0 micromol/day (Beppu, Japan) in females. The highest overall median value of taurine was found in the Japanese population samples, followed by the Chinese samples (Shanghai and Taiwan). European, North American and oceanic Caucasians, however, had much lower median values of taurine, except in the cases of the samples from France and Spain. (b) Median values of taurine were significantly associated negatively with age-adjusted IHD mortality rates across the 24 study population samples in men (R2=0.42, p<0.01), and in women (R2=0.55, p<0.01). These negative associations remained significant after adjustment for serum total cholesterol, body mass index and urinary sodium to potassium ratios. In conclusion, the study provides, for the first time, a cross-sectional database on distribution of 24-h urinary taurine excretion in 24 population samples worldwide. A strong and inverse association between population levels of taurine excretion and IHD mortality was observed.

Participation of cyclooxygenases in cutaneous thermal nociception under non-inflamed and inflamed conditions.

OBJECTIVE AND DESIGN: Effects of cyclooxygenase inhibitors on noxious thermal stimuli were investigated in non-inflamed and inflamed rats. MATERIALS: Male Sprague-Dawley rats were used in this study. TREATMENT: Cyclooxygenase inhibitors, indomethacin, mofezolac, NS-398, and JTE-522 were administered orally at a dose of 10 mg/kg 1 h prior to and 4 h after the intravenous injection of lipopolysaccharide (1 mg/kg). METHODS: The nociceptive response was evaluated from the escape latency of foot withdrawal to the thermal stimuli with a beam of light. Expression ofcyclooxygenase was examined by reverse transcription-polymerase chain reaction. RESULTS: In normal rat, administration of indomethacin, relatively cyclooxygenase-1-selective inhibitor, mofezolac, or cyclooxygenase-2-selective inhibitors, NS-398 and JTE-522 had no effects on the escape latency against thermal stimuli. Injection of lipopolysaccharide into rat induced the expression of mRNA for cyclooxygenase-2 in the subcutaneous tissue of foot pad. The escape latency at 8 h was significantly shortened by the injection. This hyperalgesia could be reversed by pretreatment of rat with NS-398 or JTE-522, but not with mofezolac. CONCLUSIONS: Cyclooxygenases may have little participation in peripheral skin thermal nociception in non-inflamed condition, although cyclooxygenase-2 could be responsible for the hyperalgesia during inflammation induced by lipopolysaccharide.

Ethnic and environmental differences in various markers of dietary intake and blood pressure among Chinese Han and three other minority peoples of China: results from the WHO Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study.

Our aim was to examine differences in dietary intake and blood pressure (BP) and their associations in four different ethnic Chinese populations, the Han, the Uygur, the Kazak and Tibetan subjects. This study used a sub-database of the Chinese sample of the WHO-Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. The WHO-CARDIAC Study was a multicenter cross-sectional study. In each center, 100 men and 100 women aged 48-56 years were selected at random from the local population. Various markers of dietary intake and their relation with BP were studied. The results of the present study indicated the following. 1) There were significant differences in mean BP and prevalence rates of hypertension, with both being higher in the Kazak and Tibetan subjects than in Han and Uygur subjects. 2) The highest mean body mass index (BMI) was observed in the Kazak subjects, while the highest 24-h urinary sodium (Na) and sodium to potassium (Na/K) ratio excretion were observed in the Tibetan subjects. There were also significant differences in other factors, such as magnesium, 3-methylhistidine (3MH) (a biological marker of animal protein intake) and taurine (a biological marker of seafood intake) excretion levels among the four ethnic peoples. 3) In general, BMI, Na and/or Na/K ratios were positively, and 3MH/creatinine and taurine/creatinine ratios were negatively associated with BP. 4) After adjustment for age, sex and potassium, subjects with obesity (BMI > or =26 kg/m2) had significantly higher relative risk of being hypertensive (HT) than those with BMI<26 kg/m2 in the Han, Uygur and Kazak populations; and subjects with elevated sodium excretion (Na > or =244 mmol/day) had significantly higher relative risk of being HT than those with Na<244 mmol/day in the Han, Uygur and Tibetan populations. In conclusion, mean BP and prevalence rates of hypertension were significantly different among the four ethnic groups. These differences are likely to be due, at least in part, to the differences in several diet-related factors, which in turn are associated with culture and environmental differences. Different health promotion strategies might thus be emphasized in different populations.

Cardiovascular risk factors in Tanzania: a revisit.

In this assessment of cardiovascular risk factors, we examined the prevalence of selected risk factors according to the World Health Organisation (WHO) CARDIAC Study protocol and compared them with a similar study conducted more than a decade ago. The survey was carried out in Dar es Salaam (D, urban), Handeni (H, rural) and Monduli (Mo, semi-nomadic area). Subjects aged 47-57 were recruited randomly for blood pressure and anthropometrical measurements, 24 h urine collection and blood sampling. A structured questionnaire was used to obtain dietary information. The 1998 survey studied 446 subjects, while the 1987 survey included 496 men and women. The measured weight, body mass index (BMI) and prevalence of obesity (BMI > or = 30 kg/m(2)) increased significantly among women in the 1998 survey in rural Handeni and urban Dar. The overall prevalence of obesity was higher for women in the most recent survey (22.8%, P < 0.0001). Diastolic blood pressure (DBP) was higher in the most recent survey for women in Handeni. The overall prevalence of hypertension (blood pressure > 160/95 mmHg, or antihypertensive drug use), rose to 41.1% in 1998, (P < 0.001) for men and to 38.7% (P < 0.05) for women. The mean total serum cholesterol and prevalence of hypercholesterolaemia increased significantly in the most recent survey in the three studied areas. The overall prevalence of hypercholestrolaemia (serum cholesterol > 5.2 mmol/l) was higher in the 1998 survey for both men (21.8%, P < 0.0001) and women (54.0%, P < 0.0001). The mean HDL cholesterol increased significantly in the most recent survey, with a significant reduction in the mean atherogenic index, though these were still at higher levels (men 5.8, P < 0.0001; women 5.1, P < 0.0001 vs. 1987). A strong positive correlation was observed between blood pressure (SBP and DBP) and body mass index, total serum cholesterol and sodium to potassium ratio. These data suggest that for the past decade there has been an increase in the mean levels and prevalence of selected cardiovascular risk factors in Tanzania.

Increased hydroxyl radicals in the hippocampus of stroke-prone spontaneously hypertensive rats during transient ischemia and recirculation.

It has been suggested that stroke-prone spontaneously hypertensive rats (SHRSP) show vulnerability to neuronal damage following transient ischemia. To observe the effect of hydroxyl radicals on neuronal damage in the hippocampus of SHRSP during ischemia and recirculation, we measured the levels of 2,3-dihydroxybenzoic acid (2,3-DHBA), as a biological marker of hydroxyl radicals in the hippocampus of SHRSP, by high pressure liquid chromatography-electrochemical detection. The production of hydroxyl radicals in the hippocampus during the first 20 min of recirculation was a peak in all intervals. The changes in 2,3-DHBA levels during ischemia and recirculation in SHRSP were significantly higher than in Wistar-Kyoto rats. These results suggest that neuronal damage following ischemia and recirculation is, in part, caused by the increase in hydroxyl radicals during ischemia and recirculation.

The relation of oxidative DNA damage to hypertension and other cardiovascular risk factors in Tanzania.

OBJECTIVES: To clarify the mechanism of involvement of oxidative stress in hypertensives, we investigated the relationship between the marker of oxidative DNA damage, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and cardiovascular risk factors, such as hypertension and serum glycosylated hemoglobin (HbA1c), among Tanzanians aged 46-58 years who were not on antihypertensive medication. DESIGN AND METHODS: Sixty subjects (males/females, 28/ 32) were selected randomly from the subjects who completed a 24h urine collection in our epidemiological study at Dar es Salaam, Tanzania in 1998. The subjects were divided into two groups, hypertensive subjects (systolic blood pressure (SBP) > or = 140 mmHg and/or diastolic blood pressure (DBP) > or =90 mmHg) and normotensive subjects (SBP < 140 mmHg and DBP < 90 mmHg) or hyperglycemic subjects (HbA1c > or = 6.0%) and normoglycemic subjects (HbA1c < 6.0%). Biological markers from urine and blood were analyzed centrally in the WHO Collaborating Center. RESULTS: The mean levels of HbA1c and 8-OHdG were significantly higher in the hypertensive subjects than in the normotensive subjects (P < 0.05). Urinary 8-OHdG was significantly higher in hyperglycemic subjects than in normoglycemic subjects. HbA1c was positively correlated with the 24-h urinary 8-OHdG excretions (r= 0.698, P < 0.0001). CONCLUSIONS: These findings suggest oxidative DNA damage is increased in hypertensive subjects, and there is a positive correlation between the level of blood glucose estimated as HbA1c and oxidative DNA damage. Hyperglycemia related to insulin resistance in hypertension in Tanzania is associated with increased urinary 8-OHdG.

Different associations of blood pressure with 24-hour urinary sodium excretion among pre- and post-menopausal women. WHO Cardiovascular Diseases and Alimentary Comparison (WHO-CARDIAC) Study.

OBJECTIVE: Having found no definite relationship between blood pressure (BP) and 24h sodium excretion in women aged 48-56 years (in contrast to the results in men of the same age) in the WHO Cardiovascular Diseases and Alimentary Comparison (WHO-CARDIAC) Study, we analyzed the data to investigate whether the sodium-BP association differed between pre- and post-menopausal women. DESIGN AND METHODS: The WHO-CARDIAC is a multicenter cross-sectional study, involving, as of July 2000, 60 collaborating centers in 25 countries. In each center, 100 men and 100 women aged 48-56 years were selected randomly from the general population of the area. In this report, 2,212 women in 21 centers located in 17 countries worldwide, who had data on menopausal status, were studied. RESULTS: After adjustment for age, body mass index (BMI) and 24h urinary potassium excretion, 24h sodium excretion was positively and significantly associated with systolic blood pressure (SBP) [pooled regression coefficient: 0.037 (SE 0.01), P < 0.01] and with diastolic blood pressure (DBP) [0.023 (0.006), P< 0.01] in post-menopausal women. Pooled regression coefficients of sodium-BP association were not significant in pre-menopausal women (P< 0.05). Cross-center correlation analyses of the 21 centers showed that 24h sodium excretion was positively associated with SBP and DBP in both pre- and post-menopausal women, and this positive association between sodium excretion and SBP was significant in post-menopausal women (R2 = 0.23, P = 0.029). CONCLUSION: Different associations between sodium and BP were observed in women with pre- and post-menopausal status. There may be a tendency for salt sensitivity to increase at the menopause.

Effects of vitamin E and sesamin on hypertension and cerebral thrombogenesis in stroke-prone spontaneously hypertensive rats.

The preventive effects of sesamin, a lignan from sesame oil, and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). At 5 weeks of age the animals were separated into four groups: (i) a control group; (ii) a vitamin E group, which was given a 1,000 mg alpha-tocopherol/kg diet; (iii) a sesamin group, given a 1,000 mg sesamin/kg diet; and (iv) a vitamin E plus sesamin group, given a 1,000 mg alpha-tocopherol plus 1,000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administrated vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (p<0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated each of elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.

Reduced production of lactate during hypoxia and reoxygenation in astrocytes isolated from stroke-prone spontaneously hypertensive rats.

Lactate production and expressions of monocarboxylate transporter 1 (MCT1) and lactate dehydrogenase (LDH) mRNA after hypoxia and reoxygenation (H/R) were examined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using astrocytes in culture isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). The basal production of lactate in SHRSP was the same as that observed in WKY. In contrast the lactate levels in SHRSP at 1 and 6 h of reoxygenation after hypoxia were significantly lower than those observed in WKY. In addition LDH and MCT1 mRNA expressions in SHRSP were significantly less strong compared with those in WKY during H/R. These findings indicate that decreased production and slow transport of lactate in SHRSP astrocytes are involved in neuronal energy depletion and possibly encourage neuronal damage, although hereditary weakness of cortical neurons is also related to cell death during H/R.